Ictal and Interictal Panic Attacks- Diagnosis and Treatment

Behavioural Neurology
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Oct 7, 2021
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Definition of Ictal and Interictal Panic Attacks
Symptoms of panic attacks such as flashes, paresthesia, anxiety, fear , derealization and depersonalization presenting in an ictal or interictal period
  • It is difficult to distinguish the borders of an ictal (during a seizure) panic attack and interictal (between seizures) panic attack.


  • Panic disorder is prevalent in 13% of patients with epilepsy.
  • Ictal panic constitutes 60% of all psychiatric auras.
  • Post-ictal panic has been found in 10% patients with treatment resistant partial epilepsy.
  • Ictal panic is particularly associated with seizure disorders involving the medial temporal lobe and rarely with seizures of frontal and parietal lobe origin.


  • Exact mechanism is not known.
  • Neuroanatomical structure abnormalities include
    • Bilateral smaller volumes of amygdala
    • Low gray matter density of left Parahippocampal gyrus
    • Lower mean volume of both temporal lobes
    • Presynaptic and postsynaptic 5-HT1A receptor binding is reduced in the raphe, orbitofrontal and temporal cortex and the amygdala
  • Neurotransmitter function disturbances include
    • SSRIs decrease seizure frequency in a dose dependent manner which correlates with extracellular thalamic serotonergic thalamic concentration
    • Flumazenil, a benzodiazepine antagonist induces panic symptoms which suggests a pathogenic role played by GABA

Clinical Presentations [Table 1]

Table 1. Clinical Presentation
Ictal Panic Attacks
Interictal Panic Attacks
Less than 30 seconds but upto hours in complex partial status epilepticus
5-20 minutes,sometimes hours
Mild to moderate
Can worsen in severity during the postictal period with a feeling of impending doom
In both awake and sleep states
Mostly in awake states
Paroxysmal salivation which may be associated with nausea and vomiting
Range of autonomic symptoms (tachycardia, blood pressure fluctuation, diffuse diaphoresis and shortness of breath)
Partially unresponsive , later becomes totally unresponsive
Usually fully aware
Stereotypic paroxysmal event
May or may not be stereotypic

Diagnostic Investigations

  • Electroencephalographic studies by capturing the events on video-EEG and using sphenoid fluoroscopy guided electrodes to identify epileptiform activity in amygdala or mesial frontal regions
  • Brain MRI studies to check for lesion or atrophy of mesial temporal lobe or hippocampus
  • Measurement of postictal serum prolactin levels within 15 minutes to rule out psychogenic seizures
  • Thyroid function test to rule out Hyperthyroidism

Differential Diagnosis

  • Panic disorder
  • Prolonged Q-T syndrome
  • Carcinoid syndrome
  • Hypoglycemia
  • Pheochromocytoma
  • Cushing syndrome
  • Psychogenic seizures
  • Hyperthyroidism

Treatment and Management

  • Accurate diagnosis and proper management is difficult if ictal panic episodes are the only manifestation of epilepsy
  • Anti-epileptic drug with positive psychotropic properties chosen
    • Divalproex sodium - 10-15 mg/kg/day , can increase 5-10 mg/kg/week , not to exceed 60 mg/kg/day
    • Escitalopram - 5-10mg /day , can increase 5-10/mg biweekly ,not to exceed 20mg /day
    • Sertraline - 25-50mg /day , can increase 25-50/mg biweekly ,not to exceed 200 mg /day
    • Citalopram - 10mg /day , can increase 10-20/mg biweekly ,not to exceed 60mg /day
    • Carbamazepine -Maintenance dose 800-1200 mg/day. Therapeutic range 4-12 mg/L. Maximum dose of 1600 mg/day
    • Lamotrigine - Without enzyme-inducing AEDs or valproic acid Initially 25 mg for 2 weeks, then 50 mg/day for 2 weeks and after 4 weeks may increase by 50 mg/day
    • Pregabalin - 150 mg/day , not to exceed 600 mg/day
  • Consider benzodiazepines alprazolam or lorazepam for 6-8 weeks because response to antidepressant drugs may not be apparent for 4-6 weeks
  • Recommend cognitive behaviour therapy
  • Consider pre-surgical evaluation if seizures persist after two anti-epileptic drug trials.

Further Reading

Teixeira A.L. (2021) Peri-Ictal and Para-Ictal Psychiatric Phenomena: A Relatively Common Yet Unrecognized Disorder. In: . Current Topics in Behavioral Neurosciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2021_223


  • Adrienne L. Johnson, Alison C. McLeish, Paula K. Shear, Michael Privitera,Panic and epilepsy in adults: A systematic review,Epilepsy & Behavior,Volume 85,2018,Pages 115-119,ISSN 1525-5050,https://doi.org/10.1016/j.yebeh.2018.06.001.
  • Anna Scalise, Fabio Placidi, Marina Diomedi, Roberto De Simone, Gian Luigi Gigli,Panic disorder or epilepsy? A case report,Journal of the Neurological Sciences,Volume 246, Issues 1–2,2006,Pages 173-175,ISSN 0022-510X,https://doi.org/10.1016/j.jns.2006.02.017.
  • Baetz M, Bowen RC. Efficacy of divalproex sodium in patients with panic disorder and mood instability who have not responded to conventional therapy. Can J Psychiatry. 1998 Feb;43(1):73-7. doi: 10.1177/070674379804300109. PMID: 9494751.
  • Beyenburg S, Mitchell AJ, Schmidt D, Elger CE, Reuber M. Anxiety in patients with epilepsy: systematic review and suggestions for clinical management. Epilepsy Behav. 2005 Sep;7(2):161-71. doi: 10.1016/j.yebeh.2005.05.014. PMID: 16054870
  • Kaplan HI, Sadock BJ, Grebb JA. Synopsis of psychiatry. Baltimore (MD):Williams & Wilkins; 1994. p. 574
  • Lesser IM, Poland RE, Holcomb C, Rose DE. Electroencephalographic study of nighttime panic attacks. J Nerv Ment Dis. 1985 Dec;173(12):744-6. doi: 10.1097/00005053-198512000-00007. PMID: 4067597.
  • Moore D, Jefferson J. Panic disorder. 2nd edition. St Louis (MO): Mosby; 2004.
  • Nor Asyikin Fadzil, Norili Farhana Ahmad Saberi, Maruzairi Husain, Zahiruddin Othman.Ictal Fear Presenting as Panic Attacks International Medical Journal Vol. 27, No. 1, pp. 6 - 7 , February 2020 School of Medical Sciences, Universiti Sains Malaysia Kubang Kerian, 16150 Kelantan, Malaysia
  • Prevalence and clinical characteristics of postictal psychiatric symptoms in partial epilepsy Andres M. Kanner, Arnoldo Soto, Hilary Gross-Kanner Neurology Mar 2004, 62 (5) 708-713; DOI: 10.1212/01.WNL.0000113763.11862.26
  • Teixeira A.L. (2021) Peri-Ictal and Para-Ictal Psychiatric Phenomena: A Relatively Common Yet Unrecognized Disorder. In: . Current Topics in Behavioral Neurosciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2021_223
  • Wendling F, Hernandez A, Bellanger JJ, Chauvel P, Bartolomei F. Interictal to ictal transition in human temporal lobe epilepsy: insights from a computational model of intracerebral EEG. J Clin Neurophysiol. 2005;22(5):343-356.
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